This study will examine the effects of direct current (DC) electrical polarization of the
brain on thinking speed, reaction time, mood, and brain waves in healthy individuals. The
results will provide information for designing further studies to examine the safety and
effectiveness of this technique in treating certain brain diseases involving impaired
cognition (thought processing). The study consists of three experiments; participants will
take part in either one or two of the experiments.
Healthy right-handed volunteers between 18 and 80 years of age with 12 or more years of
education may be eligible for this study. Candidates will be screened with a medical and
educational history and a brief neurological examination. Participants in experiments 2 and
3 will also be screened with a verbal fluency test in which they will be asked to say as
many words beginning with certain letters as they can in 1 minute.
Participants will undergo the following procedures for the experiment(s) in which they
While resting quietly, subjects receive 20 minutes of weak electrical current stimulation or
sham stimulation with no current. For the stimulation, two gauze pads soaked with a
conducting salt solution are placed on the head-one on the left side and one above the right
eye. The current is passed between the pads and may cause an itching or tingling sensation
under the electrodes. Before and after the stimulation, the participant's reaction
time-tested by moving a finger as fast as possible at the sound of a tone-and mood are
evaluated. Some participants also have an electroencephalogram, or EEG (brain wave
recording) during the experiment. After the stimulation, participants take two brief tests
of thinking speed, and the mood and reaction time tests are repeated.
The participant sits in a chair with electrodes attached to the muscles that control
movement in a finger on the right hand. Reaction time is tested as described in experiment
1. Then, transcranial magnetic stimulation (TMS) is used to test the activity of the
brain's motor cortex (the part of the brain that controls movement). For TMS, an insulated
wire coil is placed on the subject's scalp. A brief electrical current is passed through
the coil, creating a magnetic pulse that travels through the scalp and skull and causes
small electrical currents in the brain cortex. The stimulation may cause twitching of the
right hand or arm or produce a mild snapping sensation on the scalp. During the
stimulation, the electrical activity of muscles in the right hand is recorded on a computer.
Following the TMS, DC stimulation is applied, as described in experiment 1. The
stimulation begins at a low level and is followed by repeat TMS and DC stimulation at
increasingly higher levels. This continues until there is a clear effect on the muscle
response to the magnetic pulses, or until the stimulation becomes uncomfortable. At the end
of the electrical stimulation, reaction time is tested again.
This experiment uses the average DC level that produced a change in the size of the
responses to magnetic stimulation in experiment 2. Thinking speed and reaction time are
tested during the DC stimulation, and the mood test is given before and during the
stimulation. This test does not use TMS or EEG recording.
The passage of weak DC currents across the head (DC polarization) has been done for
centuries with various effects reported. Many of the reports and studies of DC effects in
humans are, however, archaic, anecdotal, uncontrolled, or scientifically baseless.
Recently, it has been shown by objective means, in controlled experiments, that this type of
treatment has robust and lasting effects on the excitability of the motor cortex in healthy
humans. In vitro and animal experiments have revealed little about the mechanism of this
effect, but neither has convincing evidence of toxicity been found at moderate doses.
Therefore, we are becoming interested in whether this type of treatment can be used to
improve cognitive processing in individuals with brain lesions, particularly of the
prefrontal cortex. The purpose of this project is to prepare the way for clinical trials by
beginning to establish the safety of this technique in humans and then to look for
preliminary evidence of potentially useful effects on cognition when moderate doses are
applied to the prefrontal cortex. First, we propose to test the safety of 20 min of anodal
and cathodal DC applied the left prefrontal area, at 1 mV, by looking for clinical-level
effects on verbal fluency, cognitive processing speed, EEG, mood, or motor reaction speed
after exposure. The duration of exposure in this study will match the time required to
gather preliminary efficacy data in healthy controls and patients. Then, in a dose-finding
study, we propose to find the anodal DC amperage necessary for producing a clear effect on
excitability, as measured by an increase in the amplitude of the motor evoked potential to
transcranial magnetic stimulation. Then, if no significant adverse effects are in the first
two studies, a preliminary efficacy study will look for differences in these measures
between groups receiving anodal, cathodal, and sham DC of the left prefrontal cortex during
Participants will be right-handed healthy volunteers aged 18-80 with greater than or equal
to 12 years of education.
Subjects must perform within one standard deviation of the mean on screening with the
verbal fluency test.
Current serious medical or psychiatric condition of any kind.
History of any significant trauma or medical condition affecting the brain or skull.
History of epileptic seizure.
History of significant psychiatric illness, i.e. requiring medication or hospitalization.
Current use of neuroactive medication or recreational drugs.
History of attention deficit-hyperactivity disorder (ADHD), learning disorder, or any
other cognitive deficit.
Presence of metal in the head other than dental hardware.
Broken skin in the area of the stimulating electrodes.